Retinoic acid is a very effective agent for the treatment of a variety of skin conditions including, but not limited to, acne, photo aging, wrinkles, and the like. One particular retinoic acid material used for skin treatment is tretinoin (all-trans retinoic acid). While retinoic acid is a highly effective therapeutic material, it can cause a number of undesirable side effects which include skin irritation and skin thinning among others. As a consequence, topical formulations comprising retinoic acid must be used with caution, and dosage control is critical. In order to avoid adverse side effects, retinoic acid therapies often rely upon the use of topical preparations of retinoic acid precursors and derivatives.
Retinol is a member of the vitamin A family and can be converted to retinoic acid under oxidizing conditions. As is known in the art, when retinol is applied to the skin, it can bioconvert to retinoic acid, and this conversion reaction is fostered by the presence of proteins. For this reason, retinol based preparations are attractive for use as therapeutic agents for the treatment of a variety of skin conditions since they can act, controllably, to deliver retinoic acid to the skin. However, retinol is a fat-soluble material and has very low solubility in aqueous vehicles. This solubility problem has limited the use of retinol based formulations.
In some instances, in order to overcome the disadvantages of using an oil based therapeutic material, emulsified preparations of retinol have been prepared. As is understood in the art, an emulsified formulation comprises a microstructure having an oily phase disposed in a continuous, aqueous phase (oil in water emulsion) or an aqueous phase disposed in an oily, continuous phase (water in oil emulsion). In an emulsion, the first phase may be present in the form of discrete vesicles or in layered (lamellar) structures which are disposed in the continuous phases. In the context of this disclosure, all of such dual phase formulations are understood to be emulsions. A typical emulsion requires the presence of an emulsifying agent in order to prevent the phases from separating and thereby destroying the emulsion. The emulsifying agent comprises a molecule having an oleophilic portion which binds to the material comprising the oily phase and a hydrophilic portion which binds to the aqueous phase.
While emulsified preparations of retinol are known, it has been found that emulsified preparations of retinol have decreased efficacy when used as topical agents for the treatment of skin. This is because the emulsified structure inhibits the absorption of retinol by the skin and its subsequent bioconversion to the active, retinoic acid form. As a consequence, retinol based skin treatment formulations have been found to have limited utility, and hence the more risky retinoic acid based formulations are often used instead. As will be explained hereinbelow, the present invention provides aqueous-based, non-emulsified retinol preparations which are highly effective in treating various skin conditions.